{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CTAG1B (also known as NY‐ESO‐1) is a cancer/testis antigen that is normally restricted to germ cells in the testis but is aberrantly expressed in a wide range of tumors. Its unusual expression pattern makes it an excellent immunotherapeutic target, as it is capable of eliciting both robust humoral and cellular immune responses. In multiple studies, NY‐ESO‐1 expression has been shown to stimulate spontaneous CD8⁺ and CD4⁺ T‐cell responses, with these T cells exhibiting multifunctional cytokine production and cytotoxicity against tumor cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, NY‐ESO‐1 has been harnessed in clinical vaccine strategies and adoptive T‐cell transfer therapies, where its ability to induce integrated immune responses correlates with enhanced clinical outcomes in patients with melanoma, ovarian cancer, multiple myeloma, hepatocellular carcinoma, and other malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to inducing potent anti‐tumor immunity, expression levels of NY‐ESO‐1 in tumor tissues have been associated with aggressive and advanced disease characteristics, indicating its utility as a prognostic marker. Elevated NY‐ESO‐1 expression has been reported in metastatic lesions as well as in tumors with poor differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": " This dual role—both as an inducer of integrated, tumor‐specific immune responses and as a marker of tumor aggressiveness—has spurred extensive research into NY‐ESO‐1–directed immunotherapies, which aim not only to break tumor-induced immune tolerance but also to improve patient outcomes via combination strategies with other immune modulators.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julien Fourcade, Zhaojun Sun, Mourad Benallaoua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20100637"}], "href": "https://doi.org/10.1084/jem.20100637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20819923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20819923"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Junko Matsuzaki, Sacha Gnjatic, Paulette Mhawech-Fauceglia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1003345107"}], "href": "https://doi.org/10.1073/pnas.1003345107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20385810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20385810"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ian D Davis, Weisan Chen, Heather Jackson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0403572101"}], "href": "https://doi.org/10.1073/pnas.0403572101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15252201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15252201"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sacha Gnjatic, Djordje Atanackovic, Elke Jäger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1133324100"}], "href": "https://doi.org/10.1073/pnas.1133324100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12853579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12853579"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hassane M Zarour, Bernard Maillere, Vladimir Brusic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T-helper epitope recognized by Th1- and Th2-type tumor-reactive CD4+ T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11782380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11782380"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jianda Yuan, Matthew Adamow, Brian A Ginsberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1110814108"}], "href": "https://doi.org/10.1073/pnas.1110814108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21933959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21933959"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Frits van Rhee, Susann M Szmania, Fenghuang Zhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-09-3707"}], "href": "https://doi.org/10.1182/blood-2004-09-3707"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15671442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15671442"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Firouzeh Korangy, Lars A Ormandy, Jörg S Bleck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-04-0181"}], "href": "https://doi.org/10.1158/1078-0432.CCR-04-0181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15240519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15240519"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Edmund K Moon, Raghuveer Ranganathan, Evgeniy Eruslanov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blockade of Programmed Death 1 Augments the Ability of Human T Cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-15-1070"}], "href": "https://doi.org/10.1158/1078-0432.CCR-15-1070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26324743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26324743"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Benjamin Weide, Henning Zelba, Evelyna Derhovanessian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2011.40.2271"}], "href": "https://doi.org/10.1200/JCO.2011.40.2271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22529253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22529253"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Max Schnurr, Martin Orban, Neil C Robson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ISCOMATRIX adjuvant induces efficient cross-presentation of tumor antigen by dendritic cells via rapid cytosolic antigen delivery and processing via tripeptidyl peptidase II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.182.3.1253"}], "href": "https://doi.org/10.4049/jimmunol.182.3.1253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19155470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19155470"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kunle Odunsi, Achim A Jungbluth, Elisabeth Stockert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NY-ESO-1 and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14522938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14522938"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Elsa F Velazquez, Achim A Jungbluth, Molly Yancovitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)--correlation with prognostic factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Immun (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17625806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17625806"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yurika Sugita, Hisashi Wada, Shoichiro Fujita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.can-03-3070"}], "href": "https://doi.org/10.1158/0008-5472.can-03-3070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15026363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15026363"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jin-Ping Lai, Paul F Robbins, Mark Raffeld, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2012.31"}], "href": "https://doi.org/10.1038/modpathol.2012.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22388761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22388761"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yao-Tseng Chen, Dara S Ross, Rita Chiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0017876"}], "href": "https://doi.org/10.1371/journal.pone.0017876"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21437249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21437249"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Francis Mussai, Sharon Egan, Stuart Hunter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-14-3443"}], "href": "https://doi.org/10.1158/0008-5472.CAN-14-3443"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26054597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26054597"}]}]}]}